tbuckley/cabot-search huggingface dataset:
Analysis of infections and parameters of humoral immunity in patients (pts) with relapsed/refractory multiple myeloma (RRMM) treated with talquetamab (tal) monotherapy in MonumenTAL-1.
Authors: Paula Rodríguez-Otero, Carolina D. Schinke, Ajai Chari, Brea Lipe, Noa Lavi, Leo Rasche, Deeksha Vishwamitra, Sheri Skerget, Raluca Verona, Xuewen Ma, Sheetal Khedkar, Brandi Hilder, Tara J. Masterson, Michela Campagna, Thomas Renaud, Jaszianne A. Tolbert, Christoph Heuck, Marie-Anne Damiette Smit, Niels W.C.J. van de Donk
Journal: Journal of Clinical Oncology (2023)

8020 Background: Infection, a key complication of MM, may be due to patient, disease, or treatment-related factors. Immunotherapies that impact normal immune cells may increase risk of infection. Tal, a bispecific antibody with clinical benefit in pts with RRMM, targets G protein–coupled receptor family C group 5 member D (GPRC5D), a protein of unknown function with significantly higher expression on malignant versus normal plasma cells. We report the infection profile and immune function with tal in the phase (ph) 1/2 MonumenTAL-1 study (NCT03399799/NCT04634552). Methods: Pts had RRMM, were intolerant to/progressed on established therapies (ph 1), or had ≥3 prior lines of therapy (ph 2; ≥1 proteasome inhibitor/immunomodulatory drug/anti-CD38 antibody). Subcutaneous tal was given at 0.4 mg/kg QW or 0.8 mg/kg Q2W. Infections (graded by CTCAE v4.03) were treated per local guidelines. B-cell subpopulations and IgG levels were assessed from whole blood and serum samples, respectively. Results: We evaluated 339 pts on tal QW or Q2W, of whom 51 had prior T-cell redirection therapy (pTCRT); infection rates are shown in the table (median follow-up, 15.9, 10.1, and 13.1 mo, respectively). New-onset infections were most prevalent during cycles 1–2. Grade (gr) 3/4 infections observed in &gt;2 pts were pneumonia (3.5%) and UTI (2.1%) on tal QW; pneumonia (2.1%) and COVID-19 (2.1%) on tal Q2W; and pneumonia (5.9%) with pTCRT. Opportunistic infections were observed in 3.5%, 4.1%, and 5.9% of pts, respectively. Less than 1.5% of pts died from infections: COVID-19 pneumonia (n=2) and one each due to septic shock, fungal sepsis, and unknown etiology. Hypogammaglobulinemia rates by IgG values were 64.3% (tal QW), 65.5% (tal Q2W), and 70.6% (pTCRT); IVIg use was 14.7%, 12.4%, and 15.7%, respectively. CD19+ B-cell levels were stable, and there was a trend toward increased non-clonal IgG over time. Conclusions: Roughly 20% of pts had gr 3/4 infections on tal (most frequently cycles 1–2), with low rates of opportunistic infections, discontinuation, and death. Infection rates, particularly rates of fatal infections, appear lower with tal than with BCMA-targeted T-cell–based therapies. A trend toward increased non-clonal IgG suggests potential recovery of humoral immunity accompanies rapid, deep, and durable responses to tal. These results distinguish tal as an important emerging therapy for RRMM. Clinical trial information: NCT03399799 , NCT04634552 . [Table: see text]
Community resilience and its impact on chemotherapy availability: An ecological analysis.
Authors: Abdul R Shour, Ronald Anguzu, Adedayo A. Onitilo
Journal: Journal of Clinical Oncology (2023)

e18510 Background: Cancer patients' resilience influences treatment outcomes, but how community resilience at the ecological level affects hospitals that provide chemotherapy is poorly understood. Methods: Agency for Health Care Research and Quality 2019 ecological data were analyzed (N=3,232 counties). The number of hospitals with chemotherapy services (continuous) was the outcome. The exposure was community resilience- individuals who live with various risk factors (income-poverty ratio, crowding, communication barrier, household unemployment, disability, age 65+; no health insurance, vehicle access, and broadband internet access). Covariates included residential racial segregation-dissimilarity index- degree to which non-white and white residents were distributed across counties, scored 0-100 (integration-segregation) and income inequality scored 0-1 (equality-inequality), recategorized as 10th (low-risk), 11th-89 th (moderate-risk), and 90th (high-risk) percentiles and rural-urban and region. Using STATA/MPv.17, descriptive, chi-square; adjusted negative binomial regression were performed adjusting for population weight. P-values ≤0.05 were considered statistically significant. Results: Chemotherapy services were available in 38.4% of counties. The adjusted model reveals that chemotherapy availability decreased in high-risk than in low-risk resilient areas (Coef.: -1.10, 95% CI: -1.34 - -0.86), but increased in rural than in urban areas (Coef.: 0.36, 95% CI: 0.61- 0.49). Conclusions: Chemotherapy services rose in rural than urban areas and services were less likely to be provided when community resilience was low. [Table: see text]
Clinical outcomes of extramammary Paget’s disease in Korea: A multicenter, retrospective study.
Authors: Byeong Seok Sohn, Jeong Eun Kim, Miso Kim, Jung Yong Hong, Jieun Lee, Song Ee Park, Hyojeong Kim, Hyo Jin Lee, Eun Joo Kang, Soon Il Lee, In Hee Lee, Seok Jae Huh, Jeong Min Jo, Sung-nam Lim, Ho Young Kim
Journal: Journal of Clinical Oncology (2023)

e21599 Background: Extramammary Paget’s disease (EMPD) is very rare disease. Due to its rarity, there have been few clinical trials and no standard therapy to date. In this multicenter retrospective study, we investigated the treatment patterns and outcomes of Korean patients with advanced/metastatic extramammary Paget’s disease. Methods: As a retrospective multicenter study, we searched the medical record from 15 centers participating Rare Cancer Committee in Korean Cancer Study Group (KCSG). Results: A total of 54 patients were identified, and 11 patients who refused or did not receive treatments were excluded. In remaining 43 patients, 9 patients received locoregional therapy as first-line treatment and 34 patients initially received systemic chemotherapy. In 34 patients who received systemic chemotherapy as first-line treatment, cisplatin plus 5-fluorouracil was the most frequently used chemotherapy regimen (n = 19). Cisplatin plus 5-fluorouracil regimen achieved an objective response rate of 42.1% and a median PFS of 7.9 months. The next frequently used chemotherapy regimen was docetaxel monotherapy (n = 6). Docetaxel monotherapy achieved an objective response rate of 50.0% and a median PFS of 8.5 months. There was no statistical difference between the two treatments (p = 0.29). Two patients received trastuzumab plus paclitaxel regimen as first-line therapy. Both obtained partial response, with PFS of 13.0+ and 8.2+ months respectively. Seventeen patients received second-line chemotherapy for disease progression. In 17 patients who received systemic chemotherapy as second-line treatment, docetaxel monotherapy was the most frequently used chemotherapy regimen (n = 6). Docetaxel monotherapy achieved an objective response rate of 50.0% and a median PFS of 4.5 months. Two patients received trastuzumab plus paclitaxel regimen as second-line therapy. Both obtained partial response, with PFS of 8.7 and 12.7 months respectively. In 4 patients received trastuzumab plus paclitaxel during first- and second-line chemotherapy, trastuzumab plus paclitaxel achieved an objective response rate of 100% and a median PFS of 10.7+ months. Overall, most patients with advanced/metastatic extramammary Paget’s disease could receive up to median two lines of chemotherapy and obtained median overall survival of 20.8 months. Conclusions: Due to its rarity, advanced or metastatic EMPD still has no established standard treatment. Results of our study indicate that there is no significant difference between cisplatin plus 5-fluorouracil and docetaxel treatment in the first-line treatment. The combination of trastuzumab with paclitaxel has longer survival than conventional cytotoxic chemotherapy only.
Role of consolidative thoracic and prophylactic cranial radiation in extensive stage small cell lung cancer in chemo-immunotherapy era.
Authors: Jai Kumar Khatri, Rick Voland, John Charles Flickinger, Maria Tria Tirona, Toni Pacioles, Jennifer Dotson, Muhammad Omer Jamil, Khurram Anwar, Vivek Yadala, Thomas Wright, Malcolm DeCamp, Yousef Shweihat, Zani S Zander, Mark Hayden Cooper, John M. Varlotto
Journal: Journal of Clinical Oncology (2023)

8595 Background: The role of consolidative thoracic and prophylactic brain radiation in extensive stage small cell lung cancer patients is controversial. We investigated the factors associated with the use of any radiation therapy (RT) and whether Radiation has a benefit to overall survival (OS) in the total patient group and whether this benefit is the same if Chemotherapy (CT) only is used, or chemo-immunotherapy (CT-IO) is used. Methods: The NCDB database was queried from years 2017-2019. Patients receiving systemic therapy- STX (CT or CT-IO) had to have at least 6 months of follow-up and have no brain metastases at diagnosis. All RT patients had to receive upfront systemic therapy, were treated 2 to 6 months from diagnosis, and if treated to the brain received 25Gy in 10 fractions only. Multi-variate analyses (MVA) were used to determine factors associated with OS and selection for any radiation. Propensity matching for factors affecting OS were used to generate Kaplan-Meier OS curves. Log-rank tests were used to determine differences in Kaplan Meier survival curves for the effects of RT on OS. Results: The total number of patients receiving RT or systemic therapy alone as well as their median follow-ups(months(mn) were (981, 33.02mn) and (8909, 30.59mn). The median time to the start of STX and RT were 22days and 135 days respectively. MVA noted that RT had a greater effect on OS (Thoracic, Brain, Both – HRs = 0.78, 0.75, and 0.68) than other interventions including IO (HR 0.87) and palliative care without RT (HR 1.07). Selection for radiation depended significantly upon factors affecting OS(HR) including liver metastases (0.59), females (1.21), age/10yr(0.78) and Charlson co-morbidity index of &gt; 3(0.66), but did not depend upon insurance status, race, or county income/high school graduation rates. Propensity score matched OS curves noted the same effects of RT on OS whether CT or CT-IO was given. The lowest HRs were noted when both thoracic and brain RT were given (see table). Conclusions: The patient with extensive stage small cell lung cancer who reach candidacy and receive RT may have a significant improvement in OS compared to the patients treated only with CT or CT-IO. Combined thoracic and prophylactic brain RT seems to be better than either one alone. The impact of radiation whether given to one or two sites may be more beneficial than immunotherapy added to chemotherapy. [Table: see text]
Retrospective clinical analysis of circulating tumor DNA (ctDNA)–based molecular response (MR) and baseline blood-based tumor mutational burden (bTMB) for monitoring response in phase 3 trial of bintrafusp alfa vs. pembrolizumab treatment of non-small cell lung cancer (NSCLC).
Authors: Zheng Feng, Andreas Machl, Danyi Wang, Brooke Overstreet, Arielle Yablonovitch, Juergen Scheuenpflug
Journal: Journal of Clinical Oncology (2023)

9098 Background: The clinical utility of ctDNA-based approaches, such as bTMB and MR, to monitor and predict response during chemo-immunotherapy was evaluated using longitudinal cohort samples from a Phase 3 study of bintrafusp alfa versus pembrolizumab as a first-line treatment in patients with PD-L1 expressing advanced NSCLC. Methods: ctDNA was collected at baseline and day 42 after treatment with bintrafusp alfa (Q2W, 1200mg) or pembrolizumab (Q3W, 200mg). The GuardantOMNI liquid biopsy (LBx) assay was used to detect somatic alterations in 497 genes and generate bTMB from baseline, and MR scores from baseline and day 42 (n = 424 samples). bTMB and somatic alterations influencing response were explored. MR scores were calculated using the validated Guardant Response algorithm. Associations between ctDNA metrics and PFS were assessed. Results: 418/424 samples passed sequencing QC; of these, somatic mutations were detected in 236/237 baseline samples and 177/181 day 42 samples. Of 212 NSCLC patients with eligible bTMB results at baseline, 104 (49.1%) patients received bintrafusp alpha and 108 (50.9%) received pembrolizumab. bTMB high (bTMB-H) is defined as &gt;20mut/MB. In the bintrafusp alpha arm, PFS was significantly longer in patients with bTMB-H (median 8.3 months vs 2.7 months, p = 0.00086). In the pembrolizumab arm, PFS was also longer in patients with bTMB-H (median 5.65 months vs 5.5 months, p = 0.0898). Of 132 NSCLC patients with eligible MR results, 67 (50.8%) patients received bintrafusp alpha and 65 (49.2%) patients received pembrolizumab. In the bintrafusp alpha arm, molecular responders had significantly longer PFS (median 7.9 months vs 4.2 months, p = 0.00042). In the pembrolizumab arm, molecular responders also had significantly longer PFS (median 8.95 months vs 4.1 months, p = 0.00054). Conclusions: ctDNA analysis from plasma samples supported MR assessment in patients treated with ICI, indicating its utility as an adjunct to RECIST in monitoring of tumor response. Blood-based TMB-high was associated with immunotherapy treatment benefit. Analysis of b-TMB and MR allowed identification of patients with improved PFS in both treatment arms. Investigation of treatment specific TMB cut off selection and potential clinical utility of defined somatic mutations is ongoing. Clinical trial information: NCT03631706 .
Quality-of-life measurement in high-risk patients with uveal melanoma receiving adjuvant sunitinib or valproic acid.
Authors: Regine Nshimiyimana Maniraho, Scott W. Keith, Marlana M. Orloff, Rino S. Seedor, Leah Downie, Liam Hulse, Shingo Sato, Erin Sharpe-Mills, Takami Sato
Journal: Journal of Clinical Oncology (2023)

e18692 Background: Despite the successful treatment of primary uveal melanoma (UM), metastasis occurs in up to half of the patients with UM. To delay metastasis for high-risk patients with UM, adjuvant therapy with sunitinib malate or valproic acid (VPA) is used. Therefore, assessing and addressing quality of life (QOL) during adjuvant therapy is essential to mitigate interferences that may prevent these patients from adherence to the therapy protocol and impair their well-being. The objective of this study is to analyze the QOL of these patients during adjuvant therapy with sunitinib or VPA, and to explore differences by the type of adjuvant therapy, age, sex, and the duration of adjuvant therapy. Methods: We analyzed longitudinal surveys of the FACT-G completed by high-risk patients with UM who participated in the randomized phase II clinical trial cohort 1 receiving 6 months of adjuvant sunitinib or VPA and Cohort 2 receiving 12 months of adjuvant sunitinib at a single center. Data were obtained before the initiation of adjuvant therapy and at 1, 3, and 6 months in cohort 1 and at 1, 3, 6, 9, and 12 months in cohort 2. We examined whether there were associations of QOL with the type of adjuvant therapy, age category, sex, and the time of adjuvant therapy using generalized estimating equations (GEE) modeling under the autoregressive working correlation structure (AR1) indexed within subjects by time. Results: There were 720 survey responses collected from 149 UM patients. In our sample, 70.4% (Cohort 1a, n = 45 and Cohort 2, n = 60) were treated with sunitinib and 29.5% (Cohort 1b, n = 44) with VPA. There was no significant difference in the QOL between the sunitinib group 1a and the VPA group 1b (p = 0.958). There was no significant difference in the overall QOL by age range (p = 0.093). However, participants aged 18 to 44 years had significantly lower emotional well-being mean scores (15.32, 95% Cl [13.53, 17.11]) compared to participants aged 65 years and above (19.06, 95% Cl [18.27, 19.86], p &lt; 0.001) but no significant difference with participants aged 45 to 64 years (18.35, 95% Cl [17.53, 19.16], p = 0.193). There was no significant difference in the QOL by sex (p = 0.863) or trend in overall QOL means scores over time as the estimated slope of 0.02 QOL units per month was not significant (95% CI [-0.35, 0.38], p = 0.94). Conclusions: In our high-risk patients with UM, the type of adjuvant therapy, age, sex, and time of adjuvant therapy were not significantly differentiating factors for the QOL scores. Participants aged 18 to 44 years had significantly lower emotional well-being scores. We did not find enough evidence to suggest that there was a change in QOL during adjuvant therapy with sunitinib or VPA.
Empathic communication skills training: Randomized controlled trial to reduce lung cancer stigma in lung cancer care.
Authors: Jamie S. Ostroff, Jennifer C. King, Andrew Ciupek, Brittney Nichols, Charlotte Malling, Lauren Rosenthal, Smita C. Banerjee
Journal: Journal of Clinical Oncology (2023)

TPS12152 Background: Stigma is commonly experienced by people diagnosed with lung cancer and is often triggered during clinical encounters with their oncology care provider (OCP), particularly associated with routine assessment of smoking history. Lung cancer stigma is associated with gaps in quality of care as well as poorer psychological and physical health-related outcomes for patients. The overall objective of this multi-site national clinical trial is to test whether an OCP-facing training intervention in empathic communication skills (ECS) reduces stigma and distress and promotes patient engagement. Our prior pilot work has demonstrated that the ECS intervention is both feasible and efficacious to reduce stigma during clinical encounters. Methods: This NCI-funded multi-site national trial employs a cluster randomized design comparing usual care (waitlist control) with ECS training (intervention). With outreach and site recruitment support provided by GO2 for Lung Cancer and the American Cancer Society, community oncology sites (n = 16) nationwide will be randomized 1:1 to each arm. 9-11 OCPs will be recruited per site with 6 unique patients per OCP enrolled (total 54-66 patients/site). Statistical analysis will evaluate the effect of ECS training on primary OCP outcomes (e.g., empathic skill uptake) and secondary patient-reported outcomes (e.g., psychological distress). The 2.5 hour ECS training is delivered live using a videoconference platform. The didactic content covers knowledge and consequences of stigma on patients with lung cancer and in-depth review of specific ECS strategies. Participants then engage in experiential small-group role-play sessions with trained patient actors, where they are given tailored feedback by trained facilitators and their peers. Eligible sites must have at least 15 OCPs and clinic volume of at least 20 new patients with lung cancer per month. Eligible OCPs (physicians, NPs and PAs) must currently be treating and conducting outpatient clinic consultations with at least 1 patient with lung cancer per week. Eligible patients must be receiving treatment for lung cancer, English and/or Spanish speaking, currently or formerly smoking, and have had no more than 5 prior visits with the participating OCP. Currently, this trial is open to accrual and has 5 sites across the nation completing paperwork for activation. Clinical trial information: NCT05456841 .
Trends, predictors and impact of atrial fibrillation on inpatient outcomes among malignant melanoma patients: A 5-year National Inpatient Sample (NIS) study.
Authors: Ayobami Gbenga Olafimihan, Philip Onyekaoso Kanemo, Inimfon Jackson, Rafaella Litvin, Ekrem Turk, Jay Vakil, Maria Cristina Cuartas Mesa, Muhammad Bilal Ibrahim, Kunnal Batra
Journal: Journal of Clinical Oncology (2023)

e21525 Background: Malignant melanoma (MM), a very aggressive cancer, is associated with the highest mortality rate among dermatologic malignancies. Atrial fibrillation (AF) is the most common cardiac arrhythmia. Very little is reported in the literature on the association between both diseases, and there is marked paucity of studies comparing outcomes in patients with concomitant MM and AF. Methods: Retrospective cohort analyses were performed using the National Inpatient Sample (NIS) data collected between 2016 and 2020. Multivariable logistic and linear regression models were used to examine the predictors of AF and inpatient outcomes among MM patients. Results: Out of 9,760 hospitalizations with a diagnosis of MM, the overall prevalence of AF was 13.3% with an increasing trend from 10.1% in 2016 to 16.4% in 2020. MM patients with AF had similar odds (adjusted odds ratio (AOR) = 0.9; 95% confidence interval (CI) = 0.451.61) of inpatient all-cause mortality when compared to those without atrial fibrillation. However, they were more likely to have longer hospital stays (beta coefficient (β) = 1.27; 95% CI = 0.392.0) and total hospital charges (β = $12,830; 95% CI: $7041.4$25426.4) when compared to their counterparts without atrial fibrillation. Furthermore, patients with AF had a double likelihood (AOR: 1.90; 95% CI: 1.252.90) of developing an acute kidney injury (AKI). We also found that female MM patients were 50% (AOR: 0.50; 95% CI: 0.360.68) less likely to have a diagnosis of AF relative to their male counterparts. Similarly, Hispanic MM patients were significantly less likely (AOR: 0.06; 95% CI: 0.0080.459) to have AF in comparison to Non-Hispanic White patients. Conclusions: There is an increasing trend of comorbid atrial fibrillation in patients hospitalized for malignant melanoma, and this is associated with longer hospital stays and higher total hospital charges. These findings highlight the need for surveillance to enable early detection of atrial fibrillation in this population.